Comparative genomics is a powerful tool for uncovering patterns of mutations within genes targeted in human health concerns. To examine structure and function, we sequence targeted genes across multiple species to identify the pattern and rate of substitutions. This report summarizes our completion of projects, current ongoing research, and initiation of new advances with bioinformatic tools used to investigate gene function. <P>In 2006-2007, we published our study of the critical male-determining gene, sex-determining region Y (SRY), essential to male fertility not only in humans, but across all placental mammals. This study published over 100 kb of data from 37 species of cat. The results show adaptive evolution taking place within SRY and changes within the protein that are considered benign compared with those that trigger deleterious developmental changes in male reproductive organs. We have also completed and published our study screening the cat Y-chromosome for informative SNPs to be used in population based studies and comparative analyses among human, chimp, mouse and cat. <P>We have completed our project investigating the theory that genes on the X and Y chromosome evolve in very different ways from those on autosomes. We describe differential rates of genetic change between protein-coding and noncoding regions between the X- chromosome, Y-chromosome and autosomes. Our study encompasses nearly 24 kb of data from each of 37 species of cat. This will give us a broad depiction of genome evolution that can assist not only in the study of human disease but how genome evolution occurs across mammals. <P>Our ongoing initiative is the development and implementation of multiple bioinformatic methods to efficiently identify genes, map their position on mammalian X and Y chromosomes, and investigate their evolution and function. We anticipate new insights through the recent incorporation of our whole genome studies of alpaca (artiodactyls), cat and pangolin (carnivore), and our ongoing phylogenetic investigation of over 200 species of primates. Assessment of patterns of change in genes linked with human disease, including cancer, can be accomplished by comparative genomics across species.